Genetic Variation in Platelet Aggregation

The aim of the study is to test whether genetic variation in the alpha 2A adrenergic receptor affects diurnal variation in platelet aggregation.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction

Detailed Description

There is a marked diurnal fluctuation in the occurrence of acute myocardial infarction and sudden death, with peak incidences occurring in the early morning. Platelet aggregation has also been shown to increase in the early morning. The investigators will test the hypothesis that alpha 2a-adrenergic receptor (ADRA2A) genetic variation, specifically haplotype 4, affects platelet aggregation. The investigators will compare diurnal platelet aggregation in haplotype 4 subjects with subjects in the other haplotype families. In addition, the investigators will compare platelet aggregation after the cold pressor test in haplotype 4 with the other haplotype families. If there are no differences among haplotypes, then the haplotypes will be combined to analyze.

• Study Type: Observational
• Enrollment (Actual): 117

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • the Vanderbilt University General Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy subjects will be recruited by advertisement and word-of-mouth.

Description

Inclusion Criteria:

• Men and women aged 18 - 45 years inclusive.
• Women of the above age will be studied between day 1 and day 14 of a normal menstrual cycle.
• Subjects must be willing to give informed consent for the study and able to adhere to the study diet and study procedures.
• Subjects and immediate extended family up till grandparents will be Caucasians or African Americans only.
• Subjects will be free of any clinically significant disease.
• Clinical laboratory test (CBC, blood chemistry) will be within acceptable limits.

Exclusion Criteria:

• Subjects who have taken any antiplatelet, anticoagulant or procoagulant medicines within the last three weeks preceding the study.
• Subjects who have taken medications (including over the counter medications) other than oral contraceptives in the past two weeks.
• Subjects who smoke or have smoked in the past 3 months.
• Subjects who are presently or were formerly a narcotic addict or alcoholic.
• Females with a positive pregnancy test.
• Females who are breast feeding.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Healthy volunteers; Normal healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LogEC50 Platelet Aggregation	EC50 represents the epinephrine concentration that produced 50% of maximal platelet aggregation (representing sensitivity to epinephrine) EC50 values were not normally distributed and were log-transformed for analyses.	at 6am and 930am

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage, Adenosine Diphosphate (ADP) Induced Platelet Aggregation	Blood samples were taken from participants and centrifuged. Adenosine Diphosphate (ADP) at a fixed concentration of 2.5 uM was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation.	at 6am and 930am
Percentage, Collagen Induced Platelet Aggregation	Blood samples were taken from participants and centrifuged. Collagen at a fixed concentration of 2.5 ug/ml was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation.	at 6am and 930am

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: Michael Stein, MBChB, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: April 10, 2012
• First Submitted That Met QC Criteria: April 11, 2012
• First Posted (ESTIMATE): April 12, 2012

Study Record Updates

• Last Update Posted (ACTUAL): June 5, 2019
• Last Update Submitted That Met QC Criteria: June 3, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Genetics; Myocardial infarction; Platelet aggregation; cold pressor test
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: 111760

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IDP that underlie results in a publication
• IPD Sharing Time Frame: 6 months after publication

IPD Sharing Access Criteria

Access Criteria:

IPD will be shared on request made to the PI. Criteria: Data is not to be shared. Data should only be used for biomedical research. Researchers requesting access will need appropriate IRB approval and sign a data use agreement.